This Mentored Career Development Award application outlines a program of career development and research training for the applicant. The ultimate goal of the candidate is to develop as a successful independent scientist in cancer research and signaling. The career development and research plan are designed to allow the candidate to reach this goal by provide him with the necessary theoretical and methodological aspects of signal transduction, as related to cell growth and cancer, and with the necessary tools that will enable him to successfully develop an independent research career and compete for independent funding. The Mentor's candidate, Dr. Enrique Rozengurt, is an internationally recognized expert in the field of signal transduction and growth regulation with extensive experience in cancer research. The UCLA-Department of Medicine, which is the environment where the candidate will develop his training and research, offers extraordinary opportunities for intellectual interactions amid a very supportive and exciting atmosphere for the development of young scientists. The more immediate priority of the candidate is to obtain grant support in order to continue his research and growth as a scientist. [unreadable] [unreadable] The candidate's research project aims to characterize the mechanisms regulating the translocation to different cellular compartments of a signaling molecule (protein kinase D/PKD) that binds the tumor promoters phorbol esters as well as diacylglycerols and to identify its downstream targets. PKD is a member of a new family of serine/threonine kinases implicated in the regulation of a variety of cellular functions, including DNA synthesis and cell proliferation, that is a downstream effector of novel protein kinase C. The candidate will analyze the intracellular translocation properties of protein kinase PKD in response to phorbol esters and G protein-coupled receptor mitogenic agonist employing real-time imaging of fluorescent-tagged PKD expressed in normal fibroblast and pancreatic cancer cells. For the identification of proteins interacting with PKD in the different cellular compartments, the applicant plans to use mass spectrometry and peptide mass fingerprinting. Our hypothesis is that the kinase activity of PKC regulates PKD by coordinating its catalytic activation and intracellular localization. [unreadable] [unreadable]